Direct-acting antiviral therapy decreases hepatocellular carcinoma recurrence rate in cirrhotic patients with chronic hepatitis C.

BACKGROUND AND AIMS: Arrival of direct-acting antiviral agents against hepatitis C virus with high-sustained virological response rates and very few side effects has drastically changed the management of hepatitis C virus infection. The impact of direct-acting antiviral exposure on hepatocellular carcinoma recurrence after a first remission in patients with advanced fibrosis remains to be clarified. METHODS: 68 consecutive hepatitis C virus patients with a first hepatocellular carcinoma diagnosis and under remission, subsequently treated or not with a direct-acting antiviral combination, were included. Clinical, biological and virological data were collected at first hepatocellular carcinoma diagnosis, at remission and during the surveillance period. RESULTS: All patients were cirrhotic. Median age was 62 years and 76% of patients were male. Twenty-three patients (34%) were treated with direct-acting antivirals and 96% of them achieved sustained virological response. Median time between hepatocellular carcinoma remission and direct-acting antivirals initiation was 7.2 months (IQR: 3.6-13.5; range: 0.3-71.4) and median time between direct-acting antivirals start and hepatocellular carcinoma recurrence was 13.0 months (IQR: 9.2-19.6; range: 3.0-24.7). Recurrence rate was 1.7/100 person-months among treated patients vs 4.2/100 person-months among untreated patients (P=.008). In multivariate survival analysis, the hazard ratio for hepatocellular carcinoma recurrence after direct-acting antivirals exposure was 0.24 (95% confidence interval: 0.10-0.55; P<.001). CONCLUSIONS: Hepatocellular carcinoma recurrence rate was significantly lower among patients treated with direct-acting antivirals compared with untreated patients. Given the potential impact of our observation, large-scale prospective cohort studies are needed to confirm these results.

Could metabolic liver function tests predict mortality on waiting list for liver transplantation? A study on 560 patients.

BACKGROUND: Allocation of graft in liver transplantation (LT) depends mainly on Model for End Stage Liver Disease (MELD) score. We studied the prognostic ability of three metabolic liver function tests in 560 cirrhotic patients listed for transplantation, in comparison with MELD and Child-Turcotte-Pugh (CTP) scores. METHODS: Indocyanine green retention rate (ICG), aminopyrine breath test (ABT), and galactose elimination capacity were performed at the time of listing in addition to standard biological parameters. Seventy-three patients died on waiting list, 438 were transplanted, and 73 died after LT. Cox regression analysis and receiver operating characteristic curves with c-statistics were calculated after stratification according to CTP and MELD score. RESULTS: For the mortality before transplantation, c-statistics showed that ICG and ABT had a slightly better prognostic ability (0.73 and 0.68, respectively) than MELD score (0.66), and similar to CTP score (0.70). ABT's prognostic ability remained significant once the MELD score (below and above 20) had already been taken into account. Only ICG had a prognostic ability to predict the survival after LT, even after stratification according to MELD and CTP score. CONCLUSIONS: Our results strongly support that ABT and ICG may be useful in the ranking of the patients in LT list, adding prognosis information in association with MELD score.

The epidemiology of Budd-Chiari syndrome in France.

INTRODUCTION: Epidemiological data is lacking on primary Budd-Chiari syndrome (BCS) in France. METHODS: Two approaches were used: (1) A nationwide survey in specialized liver units for French adults. (2) A query of the French database of discharge diagnoses screening to identify incident cases in adults. BCS associated with cancer, alcoholic/viral cirrhosis, or occurring after liver transplantation were classified as secondary. RESULTS: Approach (1) 178 primary BCS were identified (prevalence 4.04 per million inhabitants (pmi)), of which 30 were incident (incidence 0.68 pmi). Mean age was 40 ±â€¯14 yrs. Risk factors included myeloproliferative neoplasms (MPN) (48%), oral contraceptives (35%) and factor V Leiden (16%). None were identified in 21% of patients, ≥2 risk factors in 25%. BMI was higher in the group without any risk factor (25.7 kg/m2 vs 23.7 kg/m2, p < 0.001). Approach (2) 110 incident primary BCS were admitted to French hospitals (incidence 2.17 pmi). MPN was less common (30%) and inflammatory local factors predominated (39%). CONCLUSION: The entity of primary BCS as recorded in French liver units is 3 times less common than the entity recorded as nonmalignant hepatic vein obstruction in the hospital discharge database. The former entity is mostly related to MPN whereas the latter with abdominal inflammatory diseases.

Prognostic Value of Metabolic Liver Function Tests: a Study on 711 Cirrhotic Patients.

BACKGROUND AND AIMS: The prognosis of cirrhotic patients is usually assessed by Child-Pugh and MELD scores. Metabolic liver function tests such as aminopyrine breath test (ABT) and indocyanine green clearance (IGC) have been shown to reveal hepatocellular dysfunction. The aim of this retrospective study was to compare the prognostic value of the MELD score, Child-Pugh score, ABT and IGC in a large cohort of cirrhotic patients. METHODS: Between January 1996 and June 2008, 711 cirrhotic patients were included and the primary endpoint was survival without LT. The ROC curves with c-statistics, correlation coefficient and survival were calculated. RESULTS: Metabolic function tests and scores were strongly correlated. At the time of evaluation, 111 patients had died and 520 had received a transplant. Prognostic ability (estimated by the AUROC curve) to predict survival without LT at 6 months was 0.662, 0.691, 0.738 and 0.715 for ABT, IGC, Child-Pugh score and MELD score, respectively. Similarly, at 1 year, AUROC was 0.738 for Child-Pugh score, 0.716 for MELD score, 0.693 for IGC clearance and 0.651 for ABT. CONCLUSIONS: Our results strongly confirm that IGC and ABT have a high prognostic value in cirrhotic patients, similar to Child-Pugh and MELD scores. They could be developed to routinely evaluate the prognosis of patients in addition to clinical and biochemical data.

End points of therapy in chronic hepatitis B.

This review assesses the relevance of the clinical, histological, biochemical and virological end points in the course and outcome of chronic hepatitis B. The pathway and the impact of the variation in these end points are presented, as well as their definitions. The treatment goals are discussed in terms of quality of life and survival. Prevention of the progression of the disease to cirrhosis, decompensated cirrhosis, end-stage liver disease and hepatocellular carcinoma seems to be the best approach to improve survival. As these criteria are long-term end points, easier to use end points assessed in clinical trials as efficacy objectives were also analyzed to determine whether they can be used as accurate surrogate criteria. Results of therapy were then analyzed according to the approved end points and in terms of management of chronic hepatitis B. Finally, an attempt to define new clinical end points is discussed in view of the development of more potent antiviral strategies.

Noninvasive diagnosis and prognosis of liver cirrhosis: a comparison of biological scores, elastometry, and metabolic liver function tests.

BACKGROUND: Recently, noninvasive methods for the diagnosis of liver cirrhosis have been extensively developed. We assessed the accuracy of liver stiffness measurement, aspartate aminotransferase-to-platelet ratio index (APRI) score, 13C-aminopyrine breath test, and indocyanine green plasma clearance for the diagnosis of cirrhosis in patients with chronic liver disease and for the prediction of severe complications in cirrhotic patients. METHODS: A total of 296 consecutive patients with chronic liver diseases of various causes were studied. Diagnostic accuracy was assessed by receiver operating characteristic curve analysis. RESULTS: Areas under the receiver operating characteristic curve for the diagnosis of cirrhosis were (95% confidence interval) 0.93 (0.90-0.96) for liver stiffness measurement, 0.82 (0.77-0.87) for 13C-aminopyrine breath test, and 0.81 (0.76-0.86) for APRI score. Using cutoff values of 14.1 kPa for liver stiffness, 4.15% dose/h for 13C-aminopyrine breath test, and 1 for APRI score, the positive predictive value was approximately 90% for the diagnosis of cirrhosis. Using cutoff values of 65.2 kPa for liver stiffness, 1.17% dose/h for 13C-aminopyrine breath test, 2.82 for APRI score, and 51.1% for indocyanine green plasma clearance, the positive predictive value was approximately 80% for the occurrence of severe complications among cirrhotic patients. CONCLUSION: Liver stiffness measurement, 13C-aminopyrine breath test, indocyanine green plasma clearance, and APRI score are reliable noninvasive methods for the diagnosis of cirrhosis in patients with chronic liver diseases of various causes, and are also prognostic indicators for the occurrence of severe complications in cirrhotic patients.